Five seriously ill lupus patients have seen their disease driven into remission after a single infusion of modified immune cells, in a small trial that borrows from cancer therapy to harness patients' own cells to treat the autoimmune condition.
Scientists are calling the results "spectacular" and "incredibly exciting", saying the findings may herald a new era of managing autoimmune diseases that, like cancer, are notoriously hard to treat.
Lupus is a lifelong condition that, at its worst, causes organ damage on top of disabling joint pain and affects around 1 in 1,000 people, mostly women of childbearing age.
Like many other autoimmune diseases, the root causes of lupus remain an unclear mix of genetic and environmental factors.
Symptoms such as inflammation are commonly treated with courses of steroids and immunosuppressive drugs that subdue the disease-causing elements while falling short of removing them.
That may change, though, if the promising results of a new study led by rheumatologist Georg Schett of the University of Erlangen-Nuremberg in Germany can be replicated to safely 'reset' the immune systems of more lupus patients.
Inspired by the success of cell-based therapies called chimeric antigen receptor (CAR) T-cell therapies that have delivered some stunning results in blood cancers, researchers have been methodically testing whether the approach might also work for lupus – trialing the therapy first in mice, then in one patient, and now another four.
CAR-T therapies work by harvesting a patient's immune cells and engineering them to recognize and destroy rogue cells, be they cancer cells or other immune cells, when infused back into the body.
In the case of this particular trial, the therapy was designed to hunt down hordes of faulty B cells, specifically those adorned with a cell surface protein called CD19 which in individuals with lupus pumps out autoantibodies that mistakenly latch onto the body's own cells.
Following orders, the immune system rushes in to attack those tissues, damaging organs and causing joint pain, fatigue and skin rashes.
Blood tests showed the one-time therapy wiped out the patients' misguided B cells without causing significant side effects, after which disease-causing autoantibodies dropped below detectable levels. The patients' symptoms also improved so much that months later, they no longer needed to take the medications they once did to manage their condition.
While it's too early to say whether the patients are cured, and too soon to say what fraction of lupus patients would respond to treatment, the findings are heartening.
The five patients (four women and one man) have been in remission for between 5 to 17 months, and in that time, their disease has not relapsed despite a resurgence of B cells a few months after treatment.
Crucially, those newly made B cells haven't churned out the autoantibodies their dysfunctional predecessors did, so the researchers suspect they have indeed succeeded in rebooting the patients' immune systems – although time will tell.
"We were really surprised how effective it was," Schett told STAT News journalist Isabella Cueto. "I have to say that blew us away."
Immune system function wasn't quashed entirely either. Rather, the therapy selectively hunted down antibody-producing B cells while preserving immunity to chickenpox, measles, mumps, and rubella, diseases the patients had previously been vaccinated against.
"This would seem to be the holy grail of treatment," Mark Leick, a medical oncologist at Massachusetts General Hospital who was not involved in the trial, told STAT News.
Of course, the therapy will need to be tested in larger groups of lupus patients to see whether remission lasts, and if it works for some, all or most patients. Researchers will also need to keep monitoring for known side effects of CAR-T therapy that in some blood cancer patients, can unleash systemic inflammation.
Schett's team is already planning another trial to test whether other autoimmune diseases such as rheumatoid arthritis and scleroderma, may also respond to CAR-T therapy. For several years scientists have speculated this might be possible, and now it seems a real possibility.
Another hurdle to rolling out the therapy, though, should it prove to be safe and effective for treating lupus or other autoimmune diseases, is cost.
Since CAR-T therapies are tailored to each patient, and making the modified immune cells requires special manufacturing capabilities, it might only be feasible to use CAR-T therapies as last resort for lupus patients with severe disease who don't respond to other drugs.
The study was published in Nature Medicine.